title: Radiotherapy plus concurrent or sequential temozolomide for glioblastoma in the elderly: a meta-analysis.
abstract: BACKGROUND
  Many physicians are reluctant to treat elderly glioblastoma (GBM) patients as aggressively as younger patients, which is not evidence based due to the absence of validated data from primary studies. We conducted a meta-analysis to provide valid evidence for the use of the aggressive combination of radiotherapy (RT) and temozolomide (TMZ) in elderly GBM patients.
  
  
  METHODS
  A systematic literature search was conducted using the PubMed, EMBASE and Cochrane databases. Studies comparing combined RT/TMZ with RT alone in elderly patients (≥65 years) with newly diagnosed GBM were eligible for inclusion.
  
  
  RESULTS
  No eligible randomized trials were identified. Alternatively, a meta-analysis of nonrandomized studies (NRSs) was performed, with 16 studies eligible for overall survival (OS) analysis and nine for progression-free survival (PFS) analysis. Combined RT/TMZ was shown to reduce the risk of death and progression in elderly GBM patients compared with RT alone (OS hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.48-0.72; PFS: HR 0.58, 95% CI 0.41-0.84). Evaluable patients were reported to tolerate combined treatment but certain toxicities, and especially hematological toxicities, were more frequently observed. Limited data on O6-methylguanine-DNA methyltransferase (MGMT) promoter status and quality of life were reported.
  
  
  CONCLUSIONS
  The meta-analysis of NRSs provided level 2a evidence (Oxford Centre for Evidence-Based Medicine) that combined RT/TMZ conferred a clear survival benefit on a selection of elderly GBM patients who had a favorable prognosis (e.g., extensive resection, favorable KPS). Toxicities were more frequent but acceptable. Future randomized trials are warranted to justify a definitive conclusion.
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, PR China.
authors.forename: An-an
authors.initials: AA
authors.lastname: Yin
authors.forename: Lu-hua
authors.initials: LH
authors.lastname: Zhang
authors.forename: Jin-xiang
authors.initials: JX
authors.lastname: Cheng
authors.forename: Yu
authors.initials: Y
authors.lastname: Dong
authors.forename: Bo-lin
authors.initials: BL
authors.lastname: Liu
authors.forename: Ning
authors.initials: N
authors.lastname: Han
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005909:Glioblastoma / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D000077204:Temozolomide
chemical_list: D000970:Antineoplastic Agents; D003606:Dacarbazine; D000077204:Temozolomide